Evolving treatment approaches for the management of metastatic castration-resistant prostate cancer – role of radium-223

The objective: is to determine the current role of radium-223 in the emergence of new options in the treatment of patients with metastatic castration-resistant prostate cancer. Materials and methods. Studies of ERA-223 and ALSYMPCA have identified the role of radium-223 in the treatment of prostate cancer and its impact on human health. Results. In one such study, ERA-223, it was shown that the combination of abiraterone with radium-223 did not increase survival without symptomatic skeletal events compared with abiraterone plus placebo. In addition, a higher incidence of bone fractures was observed with the combination of abiraterone and radium-223, especially in patients not receiving osteomodulators (denosumab or zoledronic acid). These results have led to some changes in the indications for the use of radium-223 in Europe and more careful attention to the state of bone structure in patients with prostate cancer. An overview of expert recommendations for the prevention and treatment of bone events, as well as the consequences of prolonged targeted therapy in patients with metastatic prostate cancer, which may improve the results of general and cancer-specific survival. Radium-223 has been shown to be an important option for patients with castration-resistant prostate cancer with bone metastases, and monitoring and maintaining bone health is an important factor in prostate cancer patients. It is established that the treatment of this category of patients should begin with androge n deprivation therapy. Conclusions. A review of the recommendations of urologists, oncologists and radiation oncologists in Europe, who specialize in the treatment of patients with advanced prostate cancer, to maintain bone health, treatment consequences and the role of radium-223 in the treatment of prostate cancer. Based on the analysis of the use of radium-223 in the current treatment of CRPD, preventive measures to maintain bone health are recommended, as well as side effects based on clinical experience.

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The role of microbiota in driving castration-resistant prostate cancer

10.26226/morressier.5f69edb69b74b699bf38c5cf ◽

2020 ◽

Author(s):

Arianna Calcinotto

Keyword(s):

Prostate Cancer ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant

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Study to Gather Information on the Safety and How Radium-223 Dichloride, an Alpha Particle-emitting Radioactive Agent, Works Under Routine Clinical Practice in Taiwan in Patients With Castration-resistant Prostate Cancer (CRPC) Which Has Spread to the Bone

Case Medical Research ◽

10.31525/ct1-nct04232761 ◽

2020 ◽

Author(s):

Keyword(s):

Prostate Cancer ◽

Clinical Practice ◽

Alpha Particle ◽

Routine Clinical Practice ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Radium 223

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AR Copy Number and AR Signaling-directed Therapies in Castrationresistant Prostate Cancer

Current Cancer Drug Targets ◽

10.2174/1568009617666171122145852 ◽

2018 ◽

Vol 18 (9) ◽

pp. 869-876

Author(s):

Samanta Salvi ◽

Vincenza Conteduca ◽

Cristian Lolli ◽

Sara Testoni ◽

Valentina Casadio ◽

...

Keyword(s):

Prostate Cancer ◽

Copy Number ◽

Clinical Trial Design ◽

Complete Information ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Anti Cancer ◽

Hormone Sensitive ◽

Predictive And Prognostic Biomarker

Background: Adaptive upregulation of Androgen Receptor (AR) is the most common event involved in the progression from hormone sensitive to Castration-Resistant Prostate Cancer (CRPC). AR signaling remains the main target of new AR signalling-directed therapies such as abiraterone and enzalutamide in CRPC patients. Objective: In this review, we discuss general mechanisms of resistance to AR-targeted therapies, with a focus on the role of AR Copy Number (CN). We reported methods and clinical applications of AR CN evaluation in tissue and liquid biopsy, thus to have a complete information regarding its role as predictive and prognostic biomarker. Conclusion: Outcomes of CRPC patients are reported to be highly variable as the consequence of tumor heterogeneity. AR CN could contribute to patient selection and tumor monitoring in CRPC treated with new anti-cancer treatment as abiraterone and enzalutamide. Further studies to investigate AR CN effect to these agents and its potential combination with other prognostic or predictive clinical factors are necessary in the context of harmonized clinical trial design.

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Interplay Between SOX9, Wnt/β-Catenin and Androgen Receptor Signaling in Castration-Resistant Prostate Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20092066 ◽

2019 ◽

Vol 20 (9) ◽

pp. 2066 ◽

Cited By ~ 12

Author(s):

Namrata Khurana ◽

Suresh C. Sikka

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Signaling Pathways ◽

Critical Role ◽

Castration Resistant Prostate Cancer ◽

Form Complex ◽

Androgen Receptor Signaling ◽

Castration Resistant ◽

Signaling Axis

Androgen receptor (AR) signaling plays a key role not only in the initiation of prostate cancer (PCa) but also in its transition to aggressive and invasive castration-resistant prostate cancer (CRPC). However, the crosstalk of AR with other signaling pathways contributes significantly to the emergence and growth of CRPC. Wnt/β-catenin signaling facilitates ductal morphogenesis in fetal prostate and its anomalous expression has been linked with PCa. β-catenin has also been reported to form complex with AR and thus augment AR signaling in PCa. The transcription factor SOX9 has been shown to be the driving force of aggressive and invasive PCa cells and regulate AR expression in PCa cells. Furthermore, SOX9 has also been shown to propel PCa by the reactivation of Wnt/β-catenin signaling. In this review, we discuss the critical role of SOX9/AR/Wnt/β-catenin signaling axis in the development and progression of CRPC. The phytochemicals like sulforaphane and curcumin that can concurrently target SOX9, AR and Wnt/β-catenin signaling pathways in PCa may thus be beneficial in the chemoprevention of PCa.

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Early alkaline phosphatase dynamics as biomarker of survival in metastatic castration-resistant prostate cancer patients treated with radium-223

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-021-05283-6 ◽

2021 ◽

Author(s):

Maarten J. van der Doelen ◽

Agnes Stockhaus ◽

Yuanjun Ma ◽

Niven Mehra ◽

Jeffrey Yachnin ◽

...

Keyword(s):

Prostate Cancer ◽

Alkaline Phosphatase ◽

Confidence Interval ◽

Surrogate Marker ◽

Response Monitoring ◽

Castration Resistant Prostate Cancer ◽

Related Event ◽

Castration Resistant ◽

Radium 223 ◽

Skeletal Related Event

Abstract Purpose Radium-223 is a life-prolonging therapy for castration-resistant prostate cancer (CRPC) patients with symptomatic bone metastases. However, validated biomarkers for response monitoring are lacking. The study aim was to investigate whether early alkaline phosphatase (ALP) dynamics after the first radium-223 injection can act as surrogate marker for overall survival (OS). Methods This retrospective multicenter study included consecutive CRPC patients treated with radium-223. Patients were divided into four subgroups based on baseline ALP level (normal/elevated) and early ALP response, defined as ≥10% ALP decrease after the first radium-223 injection. Primary endpoint was OS among the subgroups. Secondary endpoints included time to first skeletal-related event, time to ALP progression, and treatment completion rate. Results A total of 180 patients were included for analysis. Median OS was 13.5 months (95% confidence interval 11.5–15.5). Patients with elevated baseline ALP without ALP response after the first injection had significantly worse OS when compared to all other patients (median OS 7.9 months versus 15.7 months, hazard ratio 2.56, 95% confidence interval 1.73–3.80, P < 0.001). Multivariate analysis demonstrated that elevated baseline ALP without ALP response after the first injection, the number of prior systemic therapies, baseline LDH level, and baseline ECOG performance status were prognostic factors of OS. Patients with elevated baseline ALP without ALP response after the first injection had significantly shorter times to ALP progression and first skeletal-related event, and more frequently discontinued radium-223 therapy when compared to other patients. Conclusion Early treatment–induced changes in ALP after one radium-223 injection were associated with OS in metastatic CRPC patients.

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